T-Zellen-Regulation unter veränderten Schwerkraftbedingungen – Erkenntnisse aus In-vitro-Experimenten in realer und simulierter Schwerelosigkeit

Seit über 30 Jahren werden zahlreiche In-vitro-Studien an menschlichen Immunzellen im Weltall, in Parabelflügen oder mittels bodengestützter Forschungseinrichtungen durchgeführt. Studien mit T-Lymphozyten in Schwerelosigkeit zeigten deutlich, dass bereits T-Lymphozyten als einzelne Zellen empfindlich auf Veränderungen in der Schwerkraft reagieren und die Zellmorphologie sowie wichtige Zellfunktionen wie Zellproliferation, Signaltransduktion und Genexpression verändert werden. Bisher ist es jedoch noch nicht gelungen, die zugrunde liegenden Mechanismen zu lokalisieren. Um eine allgemeingültige Hypothese formulieren zu können, müssen In-vitro-Experimente durch einheitliche Standards für Zellkulturbedingungen vergleichbar werden.

For more than thirty years, a large number of in vitro studies on human immune cells have been conducted in space, during parabolic flights, and in ground-based facilities. Experiments with T-lymphocytes revealed, that even as individual cells T-lymphocytes are sensitive to alterations in gravity: cell morphology as well as important cellular functions such as cell proliferation, signal transduction and gene expression are changed. However, to date research has not yet succeeded to locate the underlying mechanisms. Additionally, to be able to formulate a general hypothesis, in vitro experiments must become comparable by uniform standards for cell culture conditions.

Key words

lymphocytes - adaptive immunity - spaceflight - signaling - gravitational biology

• Literatur

• 1 Moore D, Bie P, Oser H. Biological and medical research in space: An overview of life sciences research in microgravity. Berlin New York: Springer; 1996
• 2 Kimzey SL. Hematology and Immunology Studies. In: Johnston RS, Dietlein LF, Hrsg. Biomedical Results from Skylab: NASA SP-377. Washington; D.C: Scientific and Technical Information Office; 1977
• 3 Guéguinou N, Huin-Schohn C, Bascove M et al. Could spaceflight-associated immune system weakening preclude the expansion of human presence beyond Earth's orbit?. J Leukoc Biol 2009; 86: 1027-1038
• 4 Sonnenfeld G, Shearer WT. Immune function during space flight. Nutrition 2002; 18: 899-903
• 5 Herranz R, Anken R, Boonstra J et al. Ground-Based facilities for simulation of microgravity: organism-specific recommendations for their use, and recommended terminology. Astrobiology 2013; 13: 1-17
• 6 Cogoli A, Bechler B, Müller O, Hunzinger E. Effect of microgravity on lymphocyte activation. In: ESA Hrsg. Biorack on Spacelab D1. Paris: 1988: 89-100
• 7 Bechler B, Cogoli A, Mesland D. Lymphozyten sind schwerkraftempfindlich. Naturwissenschaften 1986; 73: 400-403
• 8 Cooper D, Pellis NR. Suppressed PHA activation of T lymphocytes in simulated microgravity is restored by direct activation of protein kinase C. J Leukoc Biol 1998; 63: 550-562
• 9 Tauber S, Hauschild S, Paulsen K et al. Signal transduction in primary human T lymphocytes in altered gravity during parabolic flight and clinostat experiments. Cell Physiol Biochem 2015; 35: 1034-1051
• 10 Ullrich O, Thiel C. Gravitational Force: Triggered Stress in Cells of the Immune System. In: Chouker A, Hrsg. Stress Challenges and Immunity in Space. Berlin Heidelberg: Springer; 2012: 187-202
• 11 Hauschild S, Tauber S, Lauber B et al. T cell regulation in microgravity – The current knowledge from in vitro experiments conducted in space, parabolic flights and ground-based facilities. Acta Astronaut 2014; 104: 365-377
• 12 Cogoli A, Tschopp A, Fuchs-Bislin P. Cell sensitivity to gravity. Science 1984; 225: 228-230
• 13 Limouse M, Manié S, Konstantinova I et al. Inhibition of phorbol ester-induced cell activation in microgravity. Exp Cell Res 1991; 197: 82-86
• 14 Chapes SK, Morrison DR, Guikema JA et al. Cytoine secretion by immune cells in space. J Leukoc Biol 1992; 52: 104-110
• 15 Pippia P, Sciola L, Gogoli-Greuter M et al. Activation signals of T lymphocytes in microgravity. J Biotechnol 1996; 47: 215-222
• 16 Cogoli-Greuter M, Meloni MA, Sciola L et al. Movements and interactions of leukocytes in microgravity. J Biotechnol 1996; 47: 279-287
• 17 Schmitt DA, Hatton JP, Emond C et al. The distribution of protein kinase C in human leukocytes is altered in microgravity. FASEB J 1996; 10: 1627-1634
• 18 Cogoli-Greuter M, Sciola L, Pippia P et al. Mitogen binding, cytoskeleton patterns and motility of T lymphocytes in microgravity. In: Cogoli A, Hrsg. Life sciences experiments performed on sounding rockets (1985–1994): Texus 11–32, Maser 3–6, Maxus 1. Noordwijk: the Netherlands: ESA Publications Division; 1997: 59-70
• 19 Lewis ML, Reynolds JL, Cubano LA et al. Spaceflight alters microtubules and increases apoptosis in human lymphocytes (Jurkat). FASEB J 1998; 12: 1007-1018
• 20 Hashemi BB, Penkala JE, Vens C et al. T cell activation responses are differentially regulated during clinorotation and in spaceflight. FASEB J 1999; 13: 2071-2082
• 21 Sciola L, Cogoli-Greuter M, Cogoli A et al. Influence of microgravity on mitogen binding and cytoskeleton in Jurkat cells. Adv Space Res 1999; 24: 801-805
• 22 Crucian BE, Cubbage ML, Sams CF. Altered cyto-kine production by specific human peripheral blood cell subsets immediately following space flight. J Interferon Cytokine Res 2000; 20
• 23 Cubano LA, Lewis ML. Fas/APO-1 protein is increased in spaceflown lymphocytes (Jurkat). Exp Gerontol 2000; 35: 389-400
• 24 Lewis ML, Cubano LA, Zhao B et al. cDNA microarray reveals altered cytoskeletal gene expression in space-flown leukemic T lymphocytes (Jurkat). FASEB J 2001; 15: 1783-1785
• 25 Schatten H, Lewis ML, Chakrabarti A. Spaceflight and clinorotation cause cytoskeleton and mitochondria changes and increases in apoptosis in cultured cells. Acta Astronaut 2001; 49: 399-418
• 26 Hatton JP, Gaubert F, Cazenave JP, Schmitt D. Microgravity modifies protein kinase C isoform translocation in the human monocytic cell line U937 and human peripheral blood T-cells. J Cell Biochem 2002; 87: 39-50
• 27 Crucian BE, Stowe RP, Pierson DL, Sams CF. Immune system dysregulation following short- vs long-duration spaceflight. Aviat Space Environ Med 2008; 79: 835-843
• 28 Paulsen K, Thiel C, Timm J et al. Microgravity-induced alterations in signal transduction in cells of the immune system. Acta Astronaut 2010; 67: 1116-1125
• 29 Thiel CS, Paulsen K, Bradacs G et al. Rapid alterations of cell cycle control proteins in human T lymphocytes in microgravity. Cell Commun Signal 2012; 10: 1-1
• 30 Chang TT, Walther I, Li CF et al. The Rel/NF-κB pathway and transcription of immediate early genes in T cell activation are inhibited by microgravity. J Leukoc Biol 2012; 92: 1133-1145
• 31 Battista N, Meloni MA, Bari M et al. 5-Lipoxygenase-dependent apoptosis of human lymphocytes in the International Space Station: data from the ROALD experiment. FASEB J 2012; 26: 1791-1798
• 32 Tauber S et al. Signal transduction in primary human T lymphocytes in altered gravity – results of the MASER-12 suborbital space flight mission. Cell Communication and Signaling 2013; 11: 32-32
• 33 Pellis NR, Goodwin TJ, Risin D et al. Changes in gravity inhibit lymphocyte locomotion through type I collagen. In vitro Cell Dev Biol Anim 1997; 33: 398-405
• 34 Walther I, Pippia P, Meloni MA et al. Simulated microgravity inhibits the genetic expression of interleukin-2 and its receptor in mitogen-activated T lymphocytes. FEBS Lett 1998; 436: 115-118
• 35 Schwarzenberg M, Pippia P, Meloni M et al. Signal transduction in T lymphocytes – a comparison of the data from space, the free fall machine and the random positioning machine. Adv Space Res 1999; 24: 793-800
• 36 Sundaresan A, Risin D, Pellis NR. Loss of signal transduction and inhibition of lymphocyte locomotion in a ground-based model of microgravity. In Vitro Cell Dev Biol Anim 2002; 38: 118-122
• 37 Galleri G, Meloni MA, Camboni MG et al. Signal transduction in T lymphocites under simulated microgravity conditions: involvement of PKC isoforms. J Gravit Physiol 2002; 9: 289-290
• 38 Sundaresan A, Risin D, Pellis NR. Modeled microgravity-induced protein kinase C isoform expression in human lymphocytes. J Appl Physiol (1985) 2004; 96: 2028-2033
• 39 Risso A, Tell G, Vascotto C et al. Activation of human T lymphocytes under conditions similar to those that occur during exposure to microgravity: A proteomics study. Proteomics 2005; 5: 1827-1837
• 40 Boonyaratanakornkit JB, Cogoli A, Li CF et al. Key gravity-sensitive signaling pathways drive T cell activation. FASEB J 2005; 19: 2020-2022
• 41 Ward NE, Pellis NR, Risin SA, Risin D. Gene expression alterations in activated human T-cells induced by modeled microgravity. J Cell Biochem 2006; 99: 1187-1202
• 42 Sundaresan A, Pellis NR. Cellular and genetic adaptation in low-gravity environments. Ann N Y Acad Sci 2009; 1161: 135-146
• 43 Simons DM, Gardner EM, Lelkes PI. Sub-mitogenic phorbol myristate acetate co-stimulation rescues the PHA-induced activation of both naïve and memory T cells cultured in the rotating-wall vessel bioreactor. Cell Biol Int 2009; 33: 882-886
• 44 Kumari R, Singh KP, Dumond Jr. JW. Simulated microgravity decreases DNA repair capacity and induces DNA damage in human lymphocytes. J Cell Biochem 2009; 107: 723-731
• 45 Singh KP, Kumari R, Dumond JW. Simulated microgravity-induced epigenetic changes in human lymphocytes. J Cell Biochem 2010; 111: 123-129
• 46 Mangala LS, Zhang Y, He Z et al. Effects of simulated microgravity on expression profile of microRNA in human lymphoblastoid cells. J Biol Chem 2011; 286: 32483-32490
• 47 Chang TT, Spurlock SM, Candelario TL et al. Space-flight impairs antigen-specific tolerance induction in vivo and increases inflammatory cytokines. FASEB J Jun 17 [Epub ahead of print] 2015;